# LNCRNA REGULATION OF GENE EXPRESSION & BEHAVIOR

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $552,717

## Abstract

PROJECT SUMMARY
Alcohol use disorder (AUD) is a major socioeconomic problem in the modern world. Acute and chronic alcohol
exposure is known to lead to system-wide changes in gene expression throughout multiple brain-regions and
cell-types. The mammalian genome is comprised of both protein-coding and non-protein-coding transcripts,
with less than 2% being protein-coding. Despite outnumbering protein-coding genes, the biological function of
most non-coding transcripts remains largely unknown. The largest class of non-coding transcripts are long
non-coding RNAs (lncRNAs), which are operationally defined as transcripts longer than 200 nucleotides in
length that do not encode for proteins. Most studies conducted to-date for lncRNAs have shown a critical role
of lncRNAs in regulation of gene expression. Additionally, lncRNAs are important for alternative splicing of
protein-coding transcripts, a biological process necessary for achieving cellular and molecular diversity of
proteins. Alternative splicing is crucial for mounting context-dependent responses of the immune system.
Chronic alcohol exposure has been previously shown to activate the neuroimmune system, altering CNS
plasticity and behavior. Astrocytes are a specialized glial cell-type, outnumbering neurons, and other glial cells
in the central nervous system (CNS). Astrocytes contiguously tile the entire CNS, playing a key role in
numerous biological functions including responding to CNS insults, activation of neuroimmune pathways, and
modulating behavior. Astrocytes are known to be involved in ethanol sensitivity and consumption; however, the
contribution of lncRNAs to regulation of neuroimmune pathways in astrocytes and ethanol-related behaviors is
unknown. This research proposal will test the overall hypothesis that the expression of lncRNAs in astrocytes
is important for coordinating ethanol-induced neuroimmune activation, alternative splicing, and ethanol-related
behaviors. Using a combination of in vitro and in vivo approaches this proposal will use advanced genomic
approaches to determine the causal relationship of lncRNAs in mediating astrocyte activation and ethanol-
related behaviors. Overall, our studies will establish novel molecular mechanisms for regulating gene
expression in response to excessive alcohol exposure and contribute to a better understanding of the
pathogenesis of AUD.

## Key facts

- **NIH application ID:** 10870022
- **Project number:** 5R01AA030257-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sean P Farris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $552,717
- **Award type:** 5
- **Project period:** 2022-09-20 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870022

## Citation

> US National Institutes of Health, RePORTER application 10870022, LNCRNA REGULATION OF GENE EXPRESSION & BEHAVIOR (5R01AA030257-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870022. Licensed CC0.

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